CN101160091B - System, method and apparatus for measuring blood flow and blood volume - Google Patents

Abstract

A method of calculating blood flow in an organ of a subject using output radiofrequency signals transmitted to the organ and input radiofrequency signals received from the organ, the method comprises determining a phase shift of the input radiofrequency signals relative to the output radiofrequency signals and using the phase shift to calculate the blood flow in the organ.

Description

Be used to measure system, the method and apparatus of blood flow and blood volume

Technical field

The present invention relates to measurement, more specifically relate to measurement to the signal of telecommunication of the health of object, for example blood volume etc. in stroke volume, cardiac output, the encephalocoele to determine blood volume or blood volume rate to the signal of telecommunication of the health of object.

Background technology

Heart disease is main the causing a disease and the cause of death of Modern World.Usually, heart disease may be caused by following reason: (i) autonomic nervous system defective, wherein can not provide the normal heart rate and/or the (ii) undercapacity of cardiac muscle self from the pulse of central nervous system's control cardiac muscle, even wherein the patient has normal heart rate, its contractility also is insufficient.In any case blood volume or the supply rate supplied with by ill heart are abnormal, and what have recognized that is to be particular importance to the estimation of patient's recurrent state.

The simplest measurement, for example heart rate and blood pressure may be enough for many patients, if but have Cardiovascular abnormality, then need more detailed measurement.

Cardiac output (CO) is by the blood volume of heart pumping during typically being one minute interval.Cardiac output is the blood volume of heart rate (HR) and each heartbeat pumping, also is known as the product of stroke volume (SV).For example, for most of adults, stroke volume when static standing position on average 60 and 80ml blood between.Therefore, during the static heart rate of per minute 80 times, static cardiac output changes between 4.8 and 6.4 liters/minute.

Common clinical problem is hypotension (blood pressure is low); This may be because cardiac output be low and/or take place because of low systemic vascular resistance.This problem may take place among the patient on a large scale, particularly those patients in Intensive Care Therapy or the high dependency of postoperative unit.In these high-risk patients, typically set up more detailed monitoring, comprise through the measurement of the central venous pressure of central vein conduit with through the continuous demonstration of the arteriotony of peripheral arterial conduit.

Except that above measurement, kinemic measurement is of crucial importance.For example, when combining with arterial pressure measurement, cardiac output can be used for computing system vascular resistance.Kinemic measurement is useful for the initial cardiovascular status of setting up the patient and the response multiple treatment interfered for monitoring, and treatment is interfered for example blood transfusion, influence the inculcating of the inculcating of medicine, the active medicine of vascular (to increase or to reduce systemic vascular resistance) of muscle contraction or pharmacology ground or change heart rate by the adjusting pacing rate.

At present cicada several measure kinemic method.Such method is known as the Fick method, and this method is described in 1870 by Adolf Fick.The method equals the oxygen amount that sucked by lung based on observe oxygen amount that blood obtained by lung the time between respiratory period, in the method for Fick, measured in the oxygen amount that sucks by health between respiratory period and the difference of the oxygen concentration between venous blood and the arterial blood, and use these measured values to calculate the blood volume of pumping, should equal cardiac output by the blood volume of lung by lung.More specifically, in the method for Fick, cardiac output equals the ratio between oxygen consumption and the arteriovenous oxygen content difference.

Typically non-intervention ground measurement of oxygen consumption at the mouth place, and blood concentration is measured from blended vein and peripheral arterial blood figure.Oxygen consumption is derived by the oxygen concentration difference between expired gas capacity in measuring during certain hour and expired gas and the suction gas.

The method of Fick has many shortcomings.At first, because around the leakage of face shield or mouthful part, it is difficult collecting gas accurately, unless the patient has endotracheal pipe.The second, be problematic for the analysis (if suck gas is air, and it is simple) of the gas of the oxygen containing air of richness.The 3rd, arteriovenous oxygen content difference has proposed further problem, and problem is to measure mixed venous (being pulmonary artery) oxygen content, and therefore needs pulmonary artery catheter to be used to obtain sample, and this may cause patient's complication.

The principle of Fick method also can be with CO ₂Replace oxygen to use, promptly pass through measure CO ₂Eliminate, this may more easily determine than oxygen consumption.With this variation of Fick method, cardiac output and CO ₂The change of eliminating is divided by by the of short duration end-tidal CO that causes between respiratory period again ₂The ratio that is varied to.These changes are finished and are measured by pick off, and cycle sensor ground adds respiratory capacity in breathing circuit again.Though the method has been improved the ability of carrying out accurate gasmetry, it still is subjected to the most influence in the above restriction, particularly relates to the restriction around the leakage of face shield.

Another method is for by providing the transesophageal echocardiography (TOE) to multiple cardiac structure and parafunctional diagnosis and monitoring.TOE is used for measuring blood flow rate by record from hyperacoustic Doppler shift of erythrocyte reflection derives cardiac output.Obtained the time rate integrating for the blood flow of locating in certain location (for example left ventricle effuser), it is the integration of instantaneous blood flow rate during a cardiac cycle.The time rate integrating multiply by sectional area and heart rate to obtain cardiac output.Except that unusual inaccuracy, the method has following shortcoming: (i) system may only be operated by expert operator; (ii) because the size of system's probe needs the calm or anesthesia of severe; (iii) system is expensive; (iv) probe can not be configured to provide continuous cardiac output reading when no expert operator is on the scene.

US Patent No 6,485,431 have disclosed relative simple method, wherein are used to calculate the time constant of the interim Arterial system of mean arterial pressure and diastole by the arterial pressure of pressure cuff or manometry.The compliance of Arterial system determines from form then and is used to calculate cardiac output, and cardiac output calculates product for mean arterial pressure and compliance divided by time constant.Yet the method is very coarse and it only can provide rough cardiac output to estimate.

The kinemic method of measurement in addition is called thermodilution method.The method is based on such principle, and promptly cardiac output can be estimated from the dilution of salt water body under different temperatures from blood.Thermodilution method relates to fine duct is inserted into intravenous, by heart and in pulmonary artery.The temperature in the pulmonary artery that has been installed in critesistor sensing on the catheter tip.Salt water body (the approximately volume of 5ml) is promptly injected by right atrium that is positioned at heart in the conduit or near opening.Saline mixes in heart with blood and reduces temperature in the right atrium provisionally.Measure two temperature simultaneously: measured blood heat and typically measured the brinish temperature of injecting by the platinum temperature sensor by supravasal thermistor (temperature) sensor.Cardiac output is relevant on the contrary with the area of temperature decline curve below.

Place the conduit in the pulmonary artery and be expensive and have relevant risk, comprising: death; Infect; Hemorrhage; Arrhythmia; Carotid artery, thoracic duct, caval vein, air tube, right atrium, right ventricle, Bicuspid valve and Tricuspid valve and injury of pulmonary artery.Evidence has seldom shown that the placement pulmonary artery catheter has been improved survival and several evidences have shown pathogenic and the increase that causes death.

The non-interventional method of electric bio-impedance that is known as breast is at first in US Patent No 3,340, discloses and begin recently to attract concern [US Patent No 3,340,867,4,450,527,4 of medical profession and industrial quarters in 867,852,580,4,870,578,4,953,556,5,178,154,5,309,917,5,316,004,5,505,209,5,529,072,5,503,157,5,469,859,5,423,326,5,685,316,6,485,431,6,496,732 and 6,511,438; U.S. Patent application No 20020193689].The advantage of the electric bioimpedance method of breast has provided that successive cardiac output is measured and to patient's devoid of risk.

Typical bioimpedance system be included in that neck base portion place is connected to object and around the circumference of pectus at the electroded four end arrays of the circumference at the height place of xiphoid-process.When the alternating current of constant amplitude flows through upper hind neck portion and pectus belt electrode, and the voltage of the electrical impedance of breast proportional (or and admittance inversely proportional) measures between the belt electrode of inner neck portion and breast.The part that changes of the heart synchronous impedance of coordinating with stroke volume changes owing to aortal capacity in the expansion of cardiac cycle and during shrinking individually and uniquely provisionally.

The major defect of prior biological impedance system is that the bioimpedance detector of utilizing in such system requires several successive amplifier circuit levels.Each amplifier circuit is the input noise amplification of the interior detected signal of comfortable body part in the future undesirably, and the amplitude that therefore must increase the measurement electric current is to keep rational signal to noise ratio.Many amplifier circuits have required the large tracts of land on the printed circuit board (PCB) and have utilized a plurality of circuit blocks, have therefore increased the cost and the power consumption of system.The complexity of many amplifier systems has reduced the reliability of system and has increased the frequency of the maintenance that requires.

The typical printed circuit board (PCB) of bioimpedance system comprises one or more band filters, half-wave rectifying circuit and one or more low pass filter.Those skilled in the art will recognize that the bandwidth of noise level and band filter is proportional.Because the typical feature of present obtainable band filter is about 5% frequency ratio, so the considerable part of noise by band filter, therefore is integrated in the half-wave rectifying circuit.This problem is approximately 0.1% the fact and is worsened because of changing the typical case of thoracic cavity internal impedance, therefore causes the quite low signal to noise ratio for such system.

The problem of recognizing in biological impedance is the separation between cardiovascular bioimpedance signals and respiratory bioimpedance signals and the difficulty of differentiation, and wherein respiratory bioimpedance signals is typically much larger than the former.The optimization method of efficient that is used to increase biological impedance is in US Patent No 4,870, discloses in 578.In the method, the resistance that is caused by breathing changes by the clamp circuit inhibition synchronous with cardiac electrical activity.Clamp circuit is timed in the time clamper of beginning before the MS and measures voltage in the equipment to reference voltage.During the MS of heart, voltage clamp is released, and makes the bio-impedance that is caused by the heart pump action during MS change measured.Though the method provides the improvement to measurement efficient to a certain degree, but still is subjected to quite low influence on signal-to-noise ratio (SNR).

In addition, prior art is subjected to the restriction of the high substantially level of AM noise, and this has reduced the ability that accurate measurement is provided significantly.

Therefore the demand and highly favourable system, the method and apparatus that have extensively approval with the no above-mentioned restriction that is used to measure blood flow.

Summary of the invention

According to an aspect of the present invention, the method of the intraorganic blood flow of the input radio frequency calculated signals object that uses the output radiofrequency signal that is transferred to organ and receive from organ is provided, and method comprises determines that the input radio frequency signal is with respect to the phase shift of output radiofrequency signal and use phase shift to calculate intraorganic blood flow.

According to the further feature of the preferred embodiment of the following description of the present invention, use phase shift to calculate blood flow and comprise the linear relationship that uses between phase shift and the blood flow.

According to another aspect of the present invention, the equipment of the intraorganic blood flow of the input radio frequency calculated signals object that receives from the output radiofrequency signal that is transferred to organ with from organ is provided, and equipment comprises and is used for determining that the input radio frequency signal is with respect to the signal processing unit of the phase shift of output radiofrequency signal be used to use phase shift to calculate the blood flow computer of intraorganic blood flow.

According to the further feature of the preferred embodiment of the following description of the present invention, the blood flow computer can be operated to use the linear relationship between phase shift and the blood flow to calculate blood flow.

According to this bright another aspect again, the system of the intraorganic blood flow that is used for measuring object is provided, system comprises: the radio-frequency signal generator that is used to generate the output radiofrequency signal; A plurality of electrodes that are designed to be connected to subject's skin, electrode are used for the input radio frequency signal of output radio signal transmission to organ and sensing organ; Determine the signal processing unit of input radio frequency signal with respect to the phase shift of output radiofrequency signal with being used for, intraorganic blood flow has been represented in phase shift.

According to the further feature in the preferred embodiment of the following description of the present invention, signal processing unit comprises design and is configured to reduce or eliminates the envelope elimination unit of the which amplitude modulation of input radio frequency signal, so that the input radio frequency signal of constant envelope substantially to be provided.

According to the further again feature in the described preferred embodiment, signal processing unit comprises: with the blender to the small part telecommunication of radio-frequency signal generator and a plurality of electrodes, mixer design and be configured to the output radiofrequency signal is mixed with the input radio frequency signal is to provide the blended radiofrequency signal of having represented blood flow; With the electronic circuit of the part that is used for the blended radiofrequency signal of filtering, with the signal to noise ratio of the remainder that increases blended radiofrequency signal substantially.

According to the further again feature in the described preferred embodiment, system comprises that further the remainder that is used to use blended radiofrequency signal calculates the data processor of at least one amount, selects the group of this at least one amount blood flow and arterial blood flow in comprising stroke volume, cardiac output, encephalocoele.

According to the further again feature in the described preferred embodiment, system further comprise communicate by letter with data processor and can move the pacemaker of heart rate with the control object, wherein data processor is programmed to according to the value of this at least one amount pacemaker be carried out Electronic Control.

According to the further again feature in the described preferred embodiment, system further comprise communicate by letter with data processor and can move with drug administration device to the object administration medicine, wherein data processor is programmed to according to the value of this at least one amount the drug administration device be carried out Electronic Control.

According to the further feature again in the described preferred embodiment, system further comprise communicate by letter with data processor and can move to increase kinemic heart-assist device.

According to the further again feature in the described preferred embodiment, heart-assist device comprises design and is configured to limit the expansible reinforcement members of the part of heart tissue, therefore to increase cardiac output.

According to the further feature again in the described preferred embodiment, the partial design at least of a plurality of electrodes and being configured to has the constant substantially sensitivity of the signal of telecommunication by the electrode transmission and irrelevant with the orientation of electrode on object.

According to the further feature again in the described preferred embodiment, a plurality of electrodes comprise the attachment material to small part.

According to the further again feature in the described preferred embodiment, system further comprises the detector to the small part telecommunication with a plurality of electrodes, with the primary importance that is used for detected object and the voltage between the second position and be used for generating the input radio frequency signal in response to voltage, wherein the input radio frequency signal has been represented the impedance and/or the hematodinamics reactance of organ.

According to the further again feature in the described preferred embodiment, system comprises that further at least one is used for the pick off of sensing voltage, this at least one sensor design and being configured to generate its amplitude be in the organ, from organ or to the signal of the function of the blood flow of organ.

According to the further feature again in the described preferred embodiment, electronic circuit comprises the differentiator that is used to carry out at least one time diffusion, with impedance that organ is provided and/or each derivative of hematodinamics reactance.

According to the further again feature in the described preferred embodiment, differentiator is selected from the group that comprises digital differentiator and analog differentiation device.

According to the further again feature in the described preferred embodiment, system further comprises the display device that is used to show blood flow.

According to another aspect more of the present invention, the method for the intraorganic blood flow of measuring object is provided, method comprises: generate the output radiofrequency signal; With the input radio frequency signal of output radio signal transmission to organ and sensing organ; With definite input radio frequency signal with respect to the phase shift of output radiofrequency signal and use blood flow in the in-migration computer official mutually.

According to the further feature in the preferred embodiment of the following description of the present invention, use phase shift to calculate blood flow and comprise the linear relationship that uses between phase shift and the blood flow.

According to the further again feature in the described preferred embodiment, method further comprises the which amplitude modulation that reduces or eliminate the input radio frequency signal, so that the input radio frequency signal of constant envelope substantially to be provided.

According to the further again feature in the described preferred embodiment, reduction or elimination which amplitude modulation comprise keeps the phase place modulation of the input radio frequency signal of constant envelope substantially.

According to the further again feature in the described preferred embodiment, method further comprises mixes the output radiofrequency signal with the input radio frequency signal, so that the blended radiofrequency signal of having represented blood flow to be provided, and the part of the blended radiofrequency signal of filtering is with the signal to noise ratio of the remainder that increases blended radiofrequency signal substantially.

According to the further again feature in the described preferred embodiment, mixing comprises provides radio frequency and and radiofrequency difference.

According to the further feature again in the described preferred embodiment, by design and be configured to the filtering radio frequency and low pass filter come the part of the blended radiofrequency signal of filtering.

According to the further again feature in the described preferred embodiment, method further comprises amplifies the simulation of the remainder of blended radiofrequency signal.

According to the further again feature in the described preferred embodiment, method further comprises the digitized to the remainder of blended radiofrequency signal.

According to the further again feature in the described preferred embodiment, method comprises that further the remainder that uses blended radiofrequency signal calculates at least one amount, selects the group of this at least one amount blood volume and arterial blood flow in comprising stroke volume, cardiac output, encephalocoele.

According to the further again feature in the described preferred embodiment, arterial blood flow is selected from the group that comprises following item: arteria carotis externa blood flow, arteria carotis interna blood flow, ulnar artery blood flow, radial artery blood flow, brachial artery blood flow, common iliac artery blood flow, external iliac artery blood flow, back tibial artery blood flow, preceding tibial artery blood flow, peroneal artery blood flow, lateral plantar artery blood flow, medial plantar artery blood flow and deep plantar artery blood flow.

According to the further again feature in the described preferred embodiment, method further comprises the heart rate according to the value control object of this at least one amount.

According to the further again feature in the described preferred embodiment, by the heart rate of pacemaker control object.

According to the further feature again in the described preferred embodiment, method comprises that further the value of using this at least one amount selects the amount of medicine and type and will measure medicine with type to the object administration.

According to the further again feature in the described preferred embodiment, method further comprises the surgery approach position of the part that is provided to the object heart and keep the expansible reduction of heart of this part of heart on big time quantum, to increase cardiac output.

According to the further again feature in the described preferred embodiment, will export the input radio frequency signal of radio signal transmission to organ and sensing organ by a plurality of electrodes being connected to subject's skin.

According to the further again feature in the described preferred embodiment, the quantity of a plurality of electrodes is chosen as separates the input radio frequency signal substantially with selected at least one influence from the group that comprises posture change influence, breathing influence and motion effects.

According to the further again feature in the described preferred embodiment, a plurality of electrodes comprise two electrodes.

According to the further again feature in the described preferred embodiment, a plurality of electrodes comprise three electrodes.

According to the further again feature in the described preferred embodiment, a plurality of electrodes comprise four electrodes.

According to the further feature again in the described preferred embodiment, a plurality of electrodes are connected to has the constant substantially sensitivity of the signal of telecommunication by the electrode transmission and irrelevant with the orientation of electrode on object.

According to the further again feature in the described preferred embodiment, the comprising design and be configured to twine the conductive material at least one prolongation of small part of the outward sense of object to small part of a plurality of electrodes is to have the constant substantially sensitivity of the signal of telecommunication by the electrode transmission and externally the orientation on the organ is irrelevant with electrode.

According to the further again feature in the described preferred embodiment, outward sense is selected from the group that comprises breast, buttocks, thigh, neck, head, arm, forearm, abdomen, gluteus, lower limb and foot.

According to the further again feature in the described preferred embodiment, method further comprises the primary importance of detected object and the voltage between the second position and generates the input radio frequency signal in response to voltage that wherein the input radio frequency signal has been represented the impedance and/or the hematodinamics reactance of organ.

According to the further feature again in the described preferred embodiment, method further comprises carries out at least one time diffusion, with impedance that organ is provided and/or each derivative of hematodinamics reactance.

According to the further again feature in the described preferred embodiment, derivative is selected from the group that comprises first derivative and second dervative.

According to the further again feature in the described preferred embodiment, the carrying out of time diffusion realized by the process of selecting from the group that comprises numerical differentiation and analog differentiation.

According to the further again feature in the described preferred embodiment, method further comprises uses display device to show blood flow.

According to the further again feature in the described preferred embodiment, display device can show the blood flow as time function.

According to other aspect of the present invention, provide and be used for from output radiofrequency signal that is transferred to organ and the equipment of determining the intraorganic blood flow of object from the input radio frequency signal that organ receives, equipment comprises: have the envelope that designs and be configured to reduce or eliminate the which amplitude modulation of input radio frequency signal and eliminate unitary electronic circuit, so that therefore the input radio frequency signal of constant envelope substantially to be provided; Be used to use the input radio frequency signal of constant envelope substantially and determine the signal processing unit of intraorganic blood flow.

According to the further feature in the preferred embodiment of the following description of the present invention, signal processing unit designs and is configured to determine the input radio frequency signal with respect to the phase shift of the output radiofrequency signal of constant envelope substantially, and intraorganic blood flow has been represented in phase shift.

According to the further again feature in the described preferred embodiment, envelope is eliminated the unit design and is configured to keep the phase place modulation of input radio frequency signal.

According to the further again feature in the described preferred embodiment, envelope is eliminated the unit and is comprised limiting amplifier.

According to the further feature again in the described preferred embodiment, equipment further comprises and being used for the output radiofrequency signal and the blended blender of input radio frequency signal of constant envelope substantially, so that therefore blended radiofrequency signal to be provided.

According to the further feature again in the described preferred embodiment, design of electronic circuits and be configured to the part of the blended radiofrequency signal of filtering is with the signal to noise ratio of the remainder that increases blended radiofrequency signal substantially.

According to the further again feature in the described preferred embodiment, blender can move so that radio frequency and and radiofrequency difference to be provided.

According to the further feature again in the described preferred embodiment, electronic circuit comprise be used for the filtering radio frequency and low pass filter.

According to the further feature again in the described preferred embodiment, electronic circuit comprises the analog amplify circuit of the remainder that is used to amplify blended radiofrequency signal.

According to the further again feature in the described preferred embodiment, electronic circuit comprises and being used for the digitized digital converter of the remainder of blended radiofrequency signal.According to the further feature again in the described preferred embodiment, design of electronic circuits and be configured to minimize of the sensitivity of input radio frequency signal to the impedance contrast between the organ of a plurality of electrodes and object.

According to the further feature again in the described preferred embodiment, electronic circuit comprises that at least one is characterized as impedance substantially greater than the differential amplifier of the impedance contrast between the organ of a plurality of electrodes and object.

According to the further again feature in the described preferred embodiment, the signal to noise ratio increase is 10dB at least, more preferably increases 20dB at least, most preferably increases 30dB at least.

The present invention is by providing the shortcoming that has successfully solved present known configuration above prior art system, method and apparatus far away that is used to measure and/or calculate blood flow.

Unless additionally limit, technology and scientific terminology have the identical implication of implication of those skilled in the art's common sense in the field that is subordinate to the present invention as used herein for all.Can use in enforcement of the present invention or test though be similar to or be equivalent to the method and the material of these methods described here and material, suitable method and material are in following description.In the situation of conflict, patent specification comprises that qualification will work.In addition, material, method and example only are exemplary but not are intended to restrictive.

The enforcement of method and system of the present invention relates to task or the step of choosing with carrying out or finish manual or automatic or manual and Automatic Combined.In addition, the actual instrumentation of the preferred embodiment of the method according to this invention and system and equipment, several steps of choosing can be implemented by hardware or by the software on the operating system of any firmware or by their combination.For example, as hardware, the step of choosing of the present invention can be used as chip or circuit is implemented.As software, the step of choosing of the present invention will be implemented as a plurality of software instructions that the computer that has been used any suitable operating system is carried out.In any situation, the step of choosing of method and system of the present invention will be described as being carried out by the data processor of the computing platform that for example is used to carry out a plurality of instructions.

Description of drawings

The present invention only is described with reference to the drawings by example at this.Now especially in detail with reference to the accompanying drawings, what emphasize is, shown details only illustrates by example and only is used for purpose to the exemplary argumentation of the preferred embodiments of the present invention, and to be considered to description principle of the present invention the most useful and the easiest understanding and design aspect and to propose in order to provide.In this regard, be not intended to that comparison basic comprehension of the present invention is needed to illustrate in greater detail CONSTRUCTED SPECIFICATION of the present invention, description taken together with the accompanying drawings makes those skilled in the art understand how several forms of the present invention are implemented in practice.

Each figure is:

Fig. 1 is the indicative icon according to the conventional bioimpedance system of prior art teaching;

Fig. 2 is the indicative icon of the system that is used for the intraorganic blood flow of measuring object according to a preferred embodiment of the invention;

Fig. 3 is that the part that is used for filtered signal makes that the remainder of signal is the indicative icon of the electronic circuit of feature with the signal to noise ratio that increases substantially;

Fig. 4 a to Fig. 4 h be according to a preferred embodiment of the invention electrode (c, d, g and h) and the indicative icon of each position (a, b, e and f) of being attached to of electrode;

Fig. 4 i to Fig. 4 L is the indicative icon of attachment of electrodes agent according to a preferred embodiment of the invention;

Fig. 5 is the indicative icon of the equipment that is used for definite intraorganic blood flow of object according to a preferred embodiment of the invention;

Fig. 6 is the indicative icon of equipment that is used to calculate blood flow according to a preferred embodiment of the invention;

Fig. 7 is the flow chart of the method for calculating blood flow according to a preferred embodiment of the invention;

Fig. 8 is the flow chart of measurement method of blood flow in the object organ according to a preferred embodiment of the invention;

Fig. 9 a is the block diagram that is used to use the printed circuit board (PCB) of three electrode measurement blood flows;

Fig. 9 b is the block diagram that is used to use the printed circuit board (PCB) of two electrode measurement blood flows;

Fig. 9 c is the block diagram that is used to use the printed circuit board (PCB) of four electrode measurement blood flows;

Fig. 9 d is the block diagram that is used to amplify the analog amplify circuit of radiofrequency signal;

Figure 10 a to Figure 10 b shows the monitoring result of the derivative of hematodinamics reactance change and measurement thereof, the result uses the prototype system that has three electrodes that make up according to a preferred embodiment of the invention to obtain, and is used for determining stroke volume and kinemic purpose;

Figure 10 c shows the monitoring result of ECG signal, bio-impedance change, its first derivative and the second dervative of using conventional (prior art) system to obtain;

Figure 11 a to Figure 11 b shows the monitoring result of the hematodinamics reactance that prototype system obtained change that has two electrodes that use changes for blood volume in the measurement encephalocoele and the purpose of flow makes up and the derivative of measuring thereof;

Figure 12 a shows that use being used for according to a preferred embodiment of the invention determined stroke volume and kinemic purpose and the hematodinamics reactance that prototype system obtained that has four electrodes that makes up changes and the monitoring result of the derivative measured;

Figure 12 b shows the data that obtained by ECG (two leads) according to a preferred embodiment of the invention, blood wavefront (left side and right) and comprise comparison between the CO signal of its first derivative and second dervative; With

Figure 13 shows the monitoring result of the derivative that use changes for blood volume in the measurement encephalocoele and the purpose of flow has the hematodinamics reactance that prototype system the obtained change of four electrodes and measure.

The specific embodiment

The present invention is system, the method and apparatus that is used for the intraorganic blood flow of measuring object, and it can be used for determining many parameters relevant with blood flow, to be used for the purpose of medical diagnosis and/or treatment.Especially, the present invention can be used for determining blood volume and health in stroke volume, cardiac output, the encephalocoele for example but be not restricted to breast, buttocks, thigh, neck, head, arm, forearm, abdomen, gluteus, lower limb and other endarterial blood flows of interior tremulous pulse enough.

For understanding purpose of the present invention better, as illustrating in Fig. 2 to Fig. 9 of accompanying drawing b, at first reference is used for the structure and the operation of routine (the being prior art) system of definite blood flow, as illustrating in Fig. 1.

Before explaining at least one embodiment of the present invention in detail, it will be appreciated that the present invention is not restricted to elaboration or the structure and the arrangement details of illustrated parts in the following description in the accompanying drawings in it is used.The present invention can have other embodiment or implement in many ways or obtain.It will be appreciated that also wording used herein and term are used for purpose of description and should think restrictive.

With reference now to accompanying drawing,, Fig. 1 illustrates the conventional system that usually is called system 10 at this, and system 10 comprises that radio-frequency signal generator 12 is to generate the output of periodical high-frequency electric current in response to periodically controlling input signal.System 10 comprises that further output point electrode 14 is with the electric current of carrying from radio-frequency signal generator 12 outputs.Electrode 14 is connected to the position at the human body 13 of heart above and below.Figure 1 illustrates two output point electrodes that are connected to two pairs of positions, i.e. therefore first couple of A and second couple of D formed four end arrays of electrode.The electric current that is generated by radio-frequency signal generator 12 flows between the position is to A and D and because the impedance of health 13 has caused the voltage drop on section A-D.

System 10 further comprise electric bioimpedance detector 15 and four supplemantary electrodes be used to detect two additional positions being designated B and C between voltage signal, two additional positions are to respectively near to A and D, and are similar to the four end arrays that electrode 14 has formed electrode.Bioimpedance detector 15 is connected to health 13 by two input point electrodes 17.Detector 15 generates the output signal of the impedance of having represented section B-C in response to the voltage signal that is received by electrode 17.

The amplitude of voltage signal and periodic current is proportional and also and proportional to the electric bio-impedance of the tissue between A and the D (or to B and C).

It is that several milliampere root-mean-square and frequency are the high frequency electric of dozens of kilohertz that radio-frequency signal generator typically generates amplitude.

The amplitude of voltage signal is modulated by the change of body segment internal conductance rate.In the thoracic cavity, the reason of such change is the change of intrathoracic blood volume and in the orientation of main intra-arterial erythrocyte as the function of blood flow rate.The voltage signal modulation envelope be the stack that changes by the electrical conductivity that change caused of attitude, breathing, cardiac cycle, motion artifacts and electrical noise and.

Therefore by measuring impedance change Δ Z and calculating blood flow thus and determine blood flow.The ability of the measurement blood flow of system 10 and similar prior art systems depends on several supposition, and these supposition have been set up blood flow to the dependent model of impedance Z.More specifically, the change of supposing thoracic impedance is because the pulsation attribute of blood flow and can ignore the influence of ventilation (change of breast size).

Further all impedances changes of supposition are the variations because of the aortic blood capacity, and ignore pulmonary circulation and venous return is thought of as constant.Therefore, typically near Z=ρ L/A, wherein ρ is a blood resistivity to total impedance Z, and L is that distance between electrodes and A are its sectional areas.Suppose that aorta has cylinder form and the blood resistivity change is little, then the time dependence of aorta capacity V can be written as V (t)=ρ L ²/ Z (t), wherein Z (t)=ρ L/A (t).Yet, imputedly be that the non-invasive measurement of the obvious time dependence of Z (t) can not realize, and the static thoracic impedance Z of energy measurement only ₀

Under following supposition, that is: the resistivity of (i) blood is similar to the resistivity of thoracic tissues and has the cylinder form of the band single chamber parallel with aorta, Z with (ii) thoracic cavity ₀Satisfy 1/Z ₀=1/Z _c+ 1/Z _α, Z wherein _cAnd Z _αBe respectively thoracic cavity and aortal impedance.Further supposition | Z ₀-Z _c|＜1%, then the change Δ V capacity of the beating change of aorta capacity can be approximated to be Δ V=ρ L ²/ Z ₀ ²Δ Z.Because the relation between Δ V and the stroke volume SV depends on blood net flux (SV=V ₀+ inlet flow-output stream), so must set up other model with extrapolation SV.These models can comprise the independent assessment that aortic valve closes or the maximum time derivative (dZ/dt) of substitution aortic impedance _MaxSpray time T in the derivative of Δ V with paradoxical expansion: SV=d (Δ V)/dt=ρ L ²/ Z ₀ ²T (dZ/dt) _Max

It is proportional that the time-derivative of impedance and impedance change Δ Z.Yet typically, value Δ Z value Z less than impedance on amplitude that impedance changes is 2 to 4 orders of magnitude, therefore influences the measurement quality because of signal to noise ratio.The noise content of the signal that receives can by use one or more filterings low threshold value the band filter following and frequency that high threshold is above reduce.Yet the efficient of known band filter is not enough and signal that cause still has merging very a large amount of noise content within it.

In addition, the formula that more than is used to calculate SV comprises many coefficients that depend on measurement, and these coefficients help to aggravate the overall measurement error.Especially, at static impedance Z ₀Measurement, distance between electrodes L and/or the uncertainty that increased stroke volume significantly of the error in the paradoxical expansion ejection time T.

Again additionally, be subjected to sizable AM effect of noise by the impedance measurement of being undertaken by system 10 and other prior art systems, this has further increased the uncertainty of stroke volume.

Present embodiment has successfully overcome above shortcoming by providing in this system that usually is called the intraorganic blood flow that is used for measuring object of system 20.

With reference now to Fig. 2,, Fig. 2 is the indicative icon of system 20 according to a preferred embodiment of the invention.System 20 preferably includes the radio-frequency signal generator 22 that is used to generate the output radiofrequency signal.Generator 22 may be embodied as any radio-frequency signal generator, for example but be not restricted to the radio-frequency signal generator 12 of system 10.System 20 further comprises a plurality of electrodes 25 of the skin that is connected to object 21.Electrode 25 transmits the input radio frequency signal 26 of the organ that is derived from object 21 by the output radiofrequency signal 24 of generator 22 generations and sensing.

System 20 preferably includes signal processing unit 23 to be used for determining the phase shift Δ of signal 26 with respect to signal 24

The present inventor finds, has indicated intraorganic blood flow from the input signal that organ receives with respect to the phase shift of the output signal that is generated by generator 22.Therefore, according to of the present invention preferred embodiment, use phase shift to determine blood flow.

Use Δ

Determine that the advantage of blood flow is, compare blood flow and Δ with definite technology (as above system 10) of the prior art of wherein using impedance

Between relation depend on still less the amount that depends on measurement.Especially, the present inventor finds, at Δ

And have linear relationship between the blood flow, wherein proportionality coefficient comprises paradoxical expansion ejection time T.For example, stroke volume SV can use relational expression SV=const. * T * Δ

Calculate, and cardiac output CO can use relational expression CO=const. * T * Δ

* HR calculates, and wherein HR is the heart rate (being unit with the per minute number of times of beating for example) of object, and " const. " be constant, and it for example can use calibration curve to determine.As those skilled in the art will recognize that L and Z ₀Reduced uncertainty in the value that is obtained significantly from the disappearance of the formula that is used for SV and CO because do not exist in the value that obtained and with L and Z ₀The relevant error of measurement between involve.

According to a preferred embodiment of the invention, signal processing unit 23 comprises envelope elimination unit 35, and this unit 35 reduces or more preferably eliminated the which amplitude modulation of signal 26.Selectively and preferably, the phase place modulation of signal 26 has been kept in unit 35.The signal that is generated by unit 23 marks with numeral 26 ' in Fig. 2.The AM noise of very big amount has typically been carried in the input (signal 26) of eliminating unit 35 to envelope, and it can be described as signal v without limitation ₂₆=v (t) cos (wt+

(t)), this signal has comprised phase place and which amplitude modulation.According to a preferred embodiment of the invention, unit 35 generates and has the signal of constant envelope (signal 26 '), for example v substantially ₂₆'=v ₀Cos (wt+

(t)), v wherein ₀Be constant substantially.Signal 26 ' therefore represented the phase place (or frequency) of signal 26 to modulate.For example can use the amplitude of having amplified signal 26 and having limited signal 26 make the limiting amplifier of having removed which amplitude modulation form signal 26 '.The advantage of removing which amplitude modulation is that this has allowed the phase shift Δ between definite better input and output signal

Can determine phase shift to any frequency content of the spectrum of the radiofrequency signal that receives from organ.For example, in one embodiment, phase shift determines from fundamental component that preferably in another embodiment, phase shift is preferably definite from the secondary frequency content, etc.Alternatively, phase shift can use several frequency contents to determine, for example uses suitable average algorithm.

Processing unit 23 preferably includes blender 28, blender and generator 22 and electrode 25 to the small part telecommunication, be used for signal 24 and signal 26 ' mixing so that the blended radiofrequency signal 30 of having indicated blood flow to be provided.The simulation process process (for example amplifying) that depends on the selection that can before mixing, carry out, signal 24 and 26 ' can be input in the blender 28 by passage more than one.

For example, in one embodiment, signal 24 and 26 can be directly inputted to blender 28 from the terminal that is used to transmit signals to electrode 25 and transmit signals from electrode 25.In another embodiment, signal 26 can be via other unit 27 inputs that are designed to processing signals 26.In a further embodiment, signal 24 can wherein carry out some simulation process process from maker 22 inputs before mixing.

Blender 28 can be any known RF mixing, for example but be not restricted to two balanced radio frequency blenders and non-equilibrium RF mixing.According to a preferred embodiment of the invention, blended radiofrequency signal 30 comprises a plurality of radiofrequency signals, and a plurality of in one embodiment radiofrequency signals can be radio frequency and and radiofrequency difference.For example can realize radio frequency and and radiofrequency difference by selecting blender 28 to make signal 24 and signal 26 multiply each other.Because multiplying each other between two frequencies be equivalent to frequency and and difference on the frequency, so the signal of blender 28 outputs comprises the radio frequency and and the radiofrequency difference of hope.

One of ordinary skill in the art will appreciate that to produce radio frequency and be that although radio frequency and comprise the signal of having represented blood flow and the electrical noise of a great deal of, radiofrequency difference is noiseless approx with the advantage of radiofrequency difference.

Therefore, the invention provides the otherwise effective technique that is used to minimize the electrical noise relevant with so related measurement, the influence of wherein being concerned about on amplitude is than little about 2 to 4 orders of magnitude of measuring of amount.

According to a preferred embodiment of the invention, system 20 has further the comprised filtering electronic circuit 32 of part of signal 30 makes that the feature of rest parts 31 of signal 30 is to have the signal to noise ratio that increases substantially.

With reference now to Fig. 3,, Fig. 3 is the indicative icon of circuit 32.According to a preferred embodiment of the invention, circuit 32 comprises the radio-frequency component of low pass filter 34 with filtered signal 30.Low pass filter 34 blender 28 output therein and with the embodiment of difference in be useful especially, wherein the low pass filter filters out radio frequency and and stay radiofrequency difference, this radiofrequency difference is noiseless approx as described.

Low pass filter 34 can design and construct according to the radiofrequency difference of the specific system of using system 20.The design of the wisdom of wave filter 34 has reduced the noise contribution of remainder 31 substantially.For example in the bioimpedance system of routine, the much noise of the signal that receives merges in the residual signal, so the feature of this residual signal is about 2 kilo hertzs bandwidth.The present inventor finds, and by comprising output radiofrequency signal 24 and by it is mixed with input radio frequency signal 26, the characteristics of noise in consequent signal is that its bandwidth is at least one amplitude order of magnitude below the noise bandwidth of conventional system.

According to a preferred embodiment of the invention, blender 28 and circuit 32 design and are configured to increase signal to noise ratio 20dB at least, more preferably increase 25dB, most preferably increase 30dB.

Circuit 32 preferably includes the analog amplify circuit 36 of the remainder 31 that is used for amplifying signal 30.The structure of analog amplify circuit 36 and design unrestricted, as long as circuit 36 can amplifying signals 31.The non-limitative example of amplifying circuit 36 is described in further detail in example part subsequently hereinafter.

According to a preferred embodiment of the invention, circuit 32 further comprises and being used for signal 31 digitized digital converter 38.The digitized of signal 31 is for being useful by microprocessor to the further digital processing of digitized signal for example.

Additionally and preferably, circuit comprises the differentiator 40 (digital differentiator or analog differentiation device) that is used for measured impedance is carried out at least time diffusion, to obtain each derivative (for example first derivative, second dervative etc.) of impedance and/or hematodinamics reactance.Differentiator 40 can comprise any known electric function spare (for example chip) that can carry out the analog or digital differential.The time-derivative of impedance is useful for measuring stroke volume or cardiac output for example, as further describing in detail below.

Refer again to Fig. 2 now, according to a preferred embodiment of the invention, system 20 further comprises the data processor 42 that is used to use signal 31 at least one amount of calculating.Can calculate many amounts relevant, for example but be not restricted to blood volume in stroke volume, cardiac output and the encephalocoele with blood volume.System 20 may further include and is used to show preferably as the blood flow of time function and the display device 49 of other information.

According to a preferred embodiment of the invention, system 20 further comprises the detector 29 that is used to detect by the voltage drop on the part of the health of the object that the position limited of electrode 25.In response to detected voltage, detector 29 preferably generates the signal of the impedance of the appropriate section of having represented health.In this embodiment, stroke volume can be used (dZ/dt) _MaxCalculate, as being described in further detail hereinbefore.Known stroke volume, then multiplying each other by the heart rate with stroke volume and object calculates cardiac output.More preferably, detector 29 generates the signal of having represented hematodinamics reactance X.

As used herein, " hematodinamics reactance " refer to the imaginary part of impedance.The technology that is used for obtaining from total impedance imaginary part is known in the art.Typically, such obtaining on hardware view carried out, but the algorithm that is not precluded within the scope of the present invention on the software view uses.Recognize that as persons skilled in the art the hematodinamics reactance can be used for determining aforesaid phase shift Δ

The definite of blood flow who is provided by system 20 can be used for diagnosis and treatment.Therefore, according to a preferred embodiment of the invention, system 20 may further include the pacemaker 44 of communicating by letter with data processor 42.In this embodiment, data processor 42 preferably is programmed to according to the amount that calculates pacemaker 44 Electronic Control.For example, in one embodiment, data processor 42 has calculated cardiac output and has sent signal to pacemaker 44, and pacemaker 44 is controlled the heart rate of object 21 substantially in real time, to improve cardiac output.

Additionally or alternatively, system 20 also can comprise and preferably makes up and be designed to increase kinemic heart auxiliary device 48.Heart auxiliary device is well known in the art, and typically comprises the reinforcement members of the demi-inflation that limits heart tissue, makes cardiac output increase.In this embodiment, data processor 42 preferably is programmed for according to the cardiac output that calculates installing 48 Electronic Control, makes automatically to be carried out kinemicly determining and improving by system 20.

According to a preferred embodiment of the invention, system 20 can comprise the drug administration device 46 of communicating by letter with data processor 42.Device 46 is used for to object 21 administrations.In this embodiment, data processor 42 preferably is programmed for value according to the amount of calculating to installing 46 Electronic Control.For example,, then depend on the value of blood volume if the amount of calculating is a blood volume in the encephalocoele, data processor 42 to device 46 send signals and therefore control to the amount and/or the type of the medicine of object 21 administrations.

The number that is connected to the electrode of object 21 preferably be chosen as make substantially with the input radio frequency signal with for example but be not restricted to attitude and change influence, breathe undesirable influences such as influence, motion effects and separate.

For the electrode that uses according to a preferred embodiment of the invention of any number, being designed and being configured to have to the constant substantially sensitivity of the signal of telecommunication by the electrode transmission and irrelevant to small part of electrode with the orientation of electrode on object.

With reference now to Fig. 4 a to Fig. 4 h,, these figure be according to a preferred embodiment of the invention electrode 25 (Fig. 4 c, Fig. 4 d, Fig. 4 g and Fig. 4 h) and the indicative icon of each position (Fig. 4 a, Fig. 4 b, Fig. 4 e and Fig. 4 f) of being attached to of electrode 25.Fig. 4 c and Fig. 4 g show the inboard of electrode 25, and Fig. 4 d and Fig. 4 h show the outside of electrode 25.

Therefore, electrode 25 preferably includes design and is configured to twine the conductive material 50 at least one prolongation of small part of outward sense, and outward sense for example can be breast, buttocks, thigh, neck, head, arm, forearm, abdomen, gluteus, lower limb, foot etc.Selectively, electrode 25 also can comprise attachment material 52 (for example Velcro, glue etc.), so that electrode 25 is to the attachment of object 21.

What recognize is, for example the point electrode of the routine of using in bioimpedance system (for example seeing Fig. 1) is for certain location sensitivity that electrode was attached to.This sensitivity inherently little and fluctuation that cause by so pseudo-shadow of signal to noise ratio therein may with the measured comparable bioimpedance system of whole effect in be disadvantageous especially.What further recognize is, and the relevant problem of the sensitivity of little displacement is worsened when the point electrode number increases.Especially, for eight point electrodes of four end arrays existence of Fig. 1, each of point electrode helps the sensitivity to little displacement, therefore increased the uncertainty of final measured value.

According to of the present invention preferred embodiment, use the advantage of electrode 25 to be, the signal that receives from the health of object 21 does not rely on the little displacement of electrode.In addition, as being described in further detail hereinafter, the number of employed electrode is substantially less than employed number in conventional system.Be that still less the electrode of number (i) has reduced uncertain factor with what recognize; (ii) easier attachment; (iii) more comfortable for the patient.

With reference to figure 4a, in one embodiment, cervical region and two electrodes that electrode is attached to object 21 are attached to the heart below.This embodiment for example can be used for measuring and definite stroke volume and cardiac output.Yet, it should be understood that for definite stroke volume and kinemic purpose and do not get rid of other structures.Especially, can use two electrodes.Yet the present inventor finds, uses the motion effects of three electrodes more not obvious than the motion effects of using two electrodes.The preferred electrode of Shi Yonging is shown in Fig. 4 c (inboard) and Fig. 4 d (outside) in this embodiment.

With reference to figure 4b, in another embodiment, cervical region and two electrodes that two electrodes are attached to object 21 are attached to the heart below.This embodiment for example is used for measuring and definite stroke volume and cardiac output.As demonstration in example part subsequently, result's quality improves significantly when using four electrodes.The preferred electrode of Shi Yonging is shown in Fig. 4 c (inboard) and Fig. 4 d (outside) in this embodiment.

With reference to figure 4e to Fig. 4 h, in a further embodiment, be formed on one prolongation with on two electrodes can be used for determining the purpose of blood volume in the encephalocoele.Especially, as shown in Fig. 4 e, independent band (therefore, two electrodes) can twine around the forehead of object 21, or alternatively and preferably, two bands (therefore, four electrodes) can twine around the forehead of object 21 contiguously.

It should be understood that the present invention does not discharge the electrode of any number or connects structure.For example, can with anyly be combined and used in the electrode shown in Fig. 4 c to Fig. 4 d, at electrode or any other electrode shown in Fig. 4 g to Fig. 4 h, to measure any endarterial blood flow of health, for example but be not restricted to arteria carotis externa, arteria carotis interna, ulnar artery, radial artery, brachial artery, common iliac artery, external iliac artery, back tibial artery, preceding tibial artery, peroneal artery, lateral plantar artery, medial plantar artery and deep plantar artery.

When system 20 uses with other system, wish to minimize by the occupied area of electrode 25 not interfere the operation of other system.For example, in intensive care unit, object often is connected to ECG lead, arterial, central vein pipe, brain stem induced response equipment, breast pipe, GI pipe, intravenous pipe etc.Such or similarly in the situation, system 20 preferably includes littler electrode, electrode illustrates in Fig. 4 i to Fig. 4 L.

Fig. 4 i to Fig. 4 j show according to a preferred embodiment of the invention can be used for transmitting dorsal part (Fig. 4 i) and front side (Fig. 4 j) with the alite paste of sensing radiofrequency signal.Alite paste is included in the electric contact 45 of fixing and pre-determine distance therebetween, has therefore reduced any influence of distance to measuring between movable electrode.

Fig. 4 K to Fig. 4 L shows the front side (Fig. 4 K) and the dorsal part (Fig. 4 L) of another alite paste, remove because the electric contact on alite paste makes the alite paste of Fig. 4 K to Fig. 4 L can use one line to be connected to outside the system 20 by inner wire 47 interconnection, this another alite paste is similar at the alite paste shown in Fig. 4 i to Fig. 4 j.

According to another aspect of the present invention, provide the equipment of the intraorganic blood flow that is used for definite object, usually be called equipment 60 at this.Equipment 60 has the characteristic that has improved signal to noise ratio, and thereby equipment 60 can with any blood flow measurement system, for example system 20 is used in combination.

With reference now to Fig. 5,, Fig. 5 is the sketch map of equipment 60.Equipment 60 preferably includes has the electronic circuit that envelope is eliminated unit (for example the unit 35), is used to reduce or eliminate the which amplitude modulation of input radio frequency signal, as being described in further detail hereinbefore.Equipment further comprises the signal processing unit (for example the unit 23) that is used for determining blood flow in the organ.According to a preferred embodiment of the invention, signal processing unit is determined the phase shift of input signal with respect to output signal, as being described in further detail hereinbefore.

Equipment 60 may further include and is used for signal 24 and signal 26 ' blended blender 28, so that the hybrid radio frequency signal to be provided, as being described in further detail hereinbefore.As illustrating in Fig. 5, signal 24 and 26 can be input to blender 28, directly from being used to transfer signals to organ and from the terminal input of organ transmission or via unit 22 inputs.The electronic circuit of equipment 60 preferably filtering the part of hybrid radio frequency signal, make that the feature of remainder of signal is the signal to noise ratio that roughly increases, describe in detail in as mentioned.

According to other aspect of the present invention, provide the equipment 90 that is used for blood flow in the output and the organ of input radio frequency calculated signals object.

With reference now to Fig. 6,, Fig. 6 is the diagram of the simplification of equipment 90.Equipment 90 preferably includes signal processing unit (for example the unit 23) to be used for determining the input radio frequency signal with respect to the phase shift of output radiofrequency signal with comprise blood flow computer 92, and blood flow computer 92 uses phase shifts to calculate blood flow.Computer 92 preferably uses the linear relationship between blood flow and the phase shift to calculate blood flow, as being described in further detail hereinbefore.

According to another aspect more of the present invention, provide the method for calculating blood flow.Method is included in illustrated following steps in the flow chart of Fig. 7.In first step of the method that identifies by square frame 94, determine the phase shift of input signal, and in second step, use phase shift to calculate blood flow by square frame 96 signs with respect to output signal, for example use the linear relationship between phase shift and the blood flow.

According to another aspect more of the present invention, the method for the intraorganic blood flow of measuring object is provided, method is included in illustrated following steps in the flow chart of Fig. 8.Therefore, in first step, for example generated the output radiofrequency signal by radio-frequency signal generator by square frame 72 signs.In second step, the input radio frequency signal that radio signal transmission arrives organ and for example passes through electrod-array sensing organ will be exported by square frame 74 signs.

In third step, determine that input signal is used to calculate blood flow with respect to the phase shift of described output signal and with phase shift, as being described in further detail hereinbefore by square frame 75 signs.In the selectivity step by square frame 76 and square frame 78 signs in Fig. 8, output radiofrequency signal and input radio frequency signal mixed (square frame 76) are to provide mixed signal, and the part of mixed signal is by filtering (square frame 78), with the signal to noise ratio of the remainder that increases mixed signal substantially, as further describing hereinbefore.

According to a preferred embodiment of the invention, method may further include following selectivity step, and wherein each selectivity step selectivity step that can be independent of other is carried out with any combination or order.Therefore, in a selectivity step, the remainder of blended radiofrequency signal amplifies with simulateding; In another selectivity step, the remainder of blended radiofrequency signal is digitized; In another options step, calculate at least one amount (for example blood volume in stroke volume, cardiac output and the encephalocoele); In another step again, carry out at least one time diffusion, as being described in further detail hereinbefore.

Following is to be used for the selection step of embodiment described above and the technological selection value of part.

As used herein, term " approximately " refer to ± 10%.

The output radiofrequency signal on frequency preferably from about 10KHz to about 200KHz, and on amplitude from about 10mV to about 50mV; Input radio frequency signal about 70KHz preferably on frequency, and on amplitude about 20mV preferably; By the measurable typical impedance of present embodiment from about 25 ohm to about 35 ohm; The signal to noise ratio of consequent present embodiment is at least 40dB; The feature of low pass filter 34 be preferably the about 35Hz of cut-off frequency and digital converter 38 preferably with the sample rate of about 1000 sample per seconds to signal sampling.

Other purpose, advantage and novel characteristics of the present invention will become obvious to persons skilled in the art in the example that is explained as follows, these examples are not intended to restrictive.In addition, of the present invention as describe hereinbefore and as the various embodiments that in following claims part, requires and aspect each in following example, have test support.

Example

With reference now to following example,, following example with above description with the non-limiting way illustration the present invention.

Made up prototype according to the system of the intraorganic blood flow that is used for measuring object described above.

Prototype system comprises:

(a) generated frequency is that 70KHz and amplitude are the self-control radio-frequency signal generator of the output radiofrequency signal of 20mV;

(b) a plurality of electrodes as in Fig. 4 b, Fig. 4 c, Fig. 4 e and Fig. 4 f, describing; With

(c) double balanced mixer of buying from Mini-Circuits is used to provide as described in detail above radio frequency and and radiofrequency difference.

Prototype system further comprises the electronic circuit that is formed in the printed circuit board (PCB).The design and made several electronic circuits, with the dependency between result of study quality, design of electronic circuits and the number of poles.In Fig. 9 a to Fig. 9 d, schematically illustrate multiple electronic circuit.

Fig. 9 a shows the block diagram for the treatment of the electronic circuit that uses with three electrodes (seeing in the following example the cardiac output measurement result in 1).In Fig. 9 a, electrode cable is designated E ₁, E ₂And I ₁, wherein the output radiofrequency signal that is generated by radio-frequency signal generator (being designated OSC) is passed through E ₁And E ₂Output, and the input radio frequency signal of the measurement of health passes through I ₁Input.

Input signal is conducted through differential amplifier G ₁, band filter BPF and differential amplifier G ₂Input signal is conducted through differential amplifier G ₃, band filter BPF and envelope eliminate unit EEU.EEU has eliminated which amplitude modulation from input signal.Input signal and output signal are mixed by blender DMB, to form frequency and and difference on the frequency as described.Low pass filter LPF rejection frequency and and consequent signal (having carried difference on the frequency) further by other differential amplifier G ₅, G ₆And G ₇Amplify.In case amplify, then signal is digitized by the modulus digital converter and leads to processing and display unit via the usb communication interface.

Fig. 9 b shows the block diagram for the treatment of the electronic circuit that uses with blood volume measurement electrode in two encephalocoeles in 2 in the following example.Because only have two electrodes, so E ₂And I ₁Be combined to one lead I ₁

Therefore, output signal is conducted through differential amplifier G ₁, drive wave filter BPF and differential amplifier G ₂Input signal is conducted through differential amplifier G ₂, band filter BPF and envelope eliminate unit EEU, EEU eliminates which amplitude modulation from input signal.Input and output signal mixes by blender DMB, to form frequency and and difference on the frequency.Low pass filter LPF rejection frequency and and consequent signal further by other differential amplifier G ₄, G ₅And G ₆Amplify.As the situation of three electrodes, signal is digitized by the modulus digital converter and leads to processing and display unit via the usb communication interface.

Fig. 9 c shows the block diagram for the treatment of the electronic circuit that uses with four electrodes (seeing blood volume measurement result in cardiac output measurement result in the following example 3 and the encephalocoele in the example 4).Four leads are designated E ₁, E ₂, I ₁And I ₂, wherein the output signal that is generated by radio-frequency signal generator OSC is passed through E ₁And E ₂Output, and the input radio frequency signal of the measurement of health passes through I ₁And I ₂Input.In addition, four lead E ₁, E ₂, I ₁And I ₂By being designated C ₁, C ₂, C ₃And C ₄Capacitor be connected to health.

The principle of the circuit of Fig. 9 c is similar to the principle of the circuit of Fig. 9 a that has three electrodes.The advantage of the circuit of Fig. 9 c has been to use input lead I ₁And I ₂(as with the input lead I of Fig. 9 a ₁Compare), the influence of the impedance contrast between electrode and the health can be minimized.Especially, voltage drop I ₁And I ₂Influence by differential amplifier G ₃Characteristic impedance controlled, this characteristic impedance is chosen as enough big, makes any because the impedance of the contact between health and the electrode changes and G ₃The impedance phase ratio can ignore.

Fig. 9 d shows and is used in low-pass filtering and the block diagram of the analog amplify circuit of radiofrequency signal is amplified in filtering radio frequency and back.

Example 1

Use the stroke volume and the cardiac output of three electrodes to measure

Three electrodes are connected to human object, as shown in Fig. 4 a.The hematodinamics reactance is measured and be used for definite and monitoring (i) stroke volume; (ii) cardiac output.

Figure 10 a to Figure 10 b shows the monitoring result of using prototype system (using the circuit of Fig. 9 a) to obtain on the time scale of 250ms/div.Shown two waveforms in each figure of Figure 10 a to Figure 10 b, i.e. hematodinamics reactance changes the Measuring Time derivative with it.The waveform shown in Figure 10 b with compare opposite amplification at the waveform shown in Figure 10 a.

For comparing, Figure 10 c shows the monitoring result of using conventional system (GE/Cardiodynamic) to obtain.The waveform that shows in Figure 10 c is first derivative dZ/dt and the second dervative d that ECG signal, bio-impedance change Δ Z, Δ Z from the top to the bottom ² _Z/ d ² _t

It is tangible that the present invention (Figure 10 a to Figure 10 b) improves than the signal to noise ratio of conventional system (Figure 10 c).In prototype system, signal to noise ratio is 50dB, and signal to noise ratio is 20dB in conventional system.

Example 2

Use the interior blood volume of encephalocoele of two electrodes to change and flow measurement

Two electrodes are connected to human object, as shown in Fig. 4 e.The hematodinamics reactance is measured and be used for definite and interior blood volume change of monitoring encephalocoele and flow.

Figure 11 a to Figure 11 b shows the monitoring result of using prototype system (using the circuit of Fig. 9 b) to obtain on the time scale of 250ms/div.In each figure of Figure 11 a to Figure 11 b, shown two waveforms, i.e. the derivative of hematodinamics reactance change and its measurement, wherein in Figure 11 b, the hematodinamics reactance changes the vertical dimension of curve than the big twice of response curve among Figure 11 a.

As shown in Figure 11 a to Figure 11 b, obtained the good signal-to-noise of 50dB for two amounts.This routine curve is compared with example 1 and has been obtained sharper peak.This phenomenon is consistent with the physiology discovery, finds that according to this resistance of blood flow in brain is lower than substantially at intrathoracic resistance.Therefore, compare, in brain, in the response that blood flow is changed, only have little delay with the thoracic cavity.The amount that the quick response of blood flow is measured to proves therefore have spike in the curve of Figure 11 a to Figure 11 b.

Example 3

Use the stroke volume and the cardiac output of four electrodes to measure

Four electrodes are connected to human object, as shown in Fig. 4 b.The hematodinamics reactance is measured and be used for definite and monitoring (i) stroke volume; (2) cardiac output.

Figure 12 a shows the monitoring result of using prototype system (using the circuit of Fig. 9 c) to obtain on the time scale of 500ms/div.Two waveforms in Figure 12, have been shown, i.e. the time-derivative of hematodinamics reactance change and its measurement.

Figure 12 b shows according to embodiments of the invention from the CO signal of phase shift Δ φ calculating with from the comparison between the data of other passages acquisitions.Figure 12 b shows with time function from the top to the bottom: the first derivative (dN) of ECG lead I (being designated I in Figure 12 b), ECG lead II (being designated II), left blood wavefront (L), right blood wavefront (R), CO signal (N), CO signal and the second dervative (ddN) of CO signal.As shown in Figure 12 b, embodiments of the invention provide high-quality signal, and this signal has the signal to noise ratio of raising and indicated blood flow.

Comparison diagram 12a to Figure 12 b and Figure 10 a to Figure 10 b, the use of four electrodes (with the electronic circuit among Fig. 9 c) has improved result's quality significantly.

Example 4

Use the interior blood volume of encephalocoele of four electrodes to change and flow measurement

Two electrodes are connected to human object, as shown in Fig. 4 f.The hematodinamics reactance is measured and be used for definite and interior blood volume change of monitoring encephalocoele and flow.

Figure 13 shows the monitoring result of using prototype system (using the circuit of Fig. 9 c) to obtain on the time scale of 500ms/div.Two waveforms in Figure 13, have been shown, i.e. the derivative of hematodinamics reactance change and its measurement.

As shown in Figure 13, obtained the good signal-to-noise of 50dB for two amounts.As in above example 3, contrast between Figure 13 and Fig. 9 a to Fig. 9 b has disclosed the remarkable improvement of this example (circuit among four electrodes and Fig. 9 c) ratio 2 (circuit among two electrodes and Fig. 9 b).

What recognize is, of the present invention some be characterized as and in the context of the embodiment that separates, describe for the purpose of clear, these features also can be provided among the one embodiment in combination.On the contrary, various features of the present invention is described in the context of one embodiment during simplifying, and these features also can provide dividually or with any suitable sub-portfolio.

Though the present invention describes in conjunction with its certain embodiments, manyly substitute, modifications and variations will be obvious for those skilled in the art.Therefore, be intended to comprise substituting in all such spirit and scope that fall into incidental claims, modifications and variations.All publications, patent and the patent application of mentioning in this description intactly merged by being referenced in this description, and the degree of merging merges by reference to being designated as especially and individually as each independent announcement thing, patent or patent application at this.In addition, any reference in this application quotes or discerns should not be construed as and allow such reference to can be used as prior art of the present invention.

Claims (72)

1. a use is transferred to the output radio-frequency current signal of organ and the method for the intraorganic blood flow of the input radio frequency calculated signals object that receives from organ, this method comprises determines the input radio frequency signal with respect to the phase shift of output radio-frequency current signal and use described phase shift to calculate intraorganic blood flow, and wherein said calculating is based on the linear relationship between described phase shift and the blood flow.

2. method according to claim 1, the proportionality coefficient of wherein said linear relationship comprise the paradoxical expansion ejection time of object heart.

3. equipment that is used for the intraorganic blood flow of the input radio frequency calculated signals object that receives from the output radio-frequency current signal that is transferred to organ with from organ, this equipment comprises and is used for determining the input radio frequency signal with respect to the current signal processing unit of the phase shift of output radio-frequency current signal be used to use described phase shift to calculate the blood flow computer of intraorganic blood flow that wherein said blood flow computer can move to use the linear relationship between described phase shift and the blood flow to calculate blood flow.

4. equipment according to claim 3, the proportionality coefficient of wherein said linear relationship comprise the paradoxical expansion ejection time of object heart.

5. system that is used for the intraorganic blood flow of measuring object, this system comprises:

Be used to generate the radio-frequency signal generator of output radiofrequency signal;

A plurality of electrodes that are designed to be connected to subject's skin, described electrode are used for the input radio frequency signal of output radio signal transmission to organ and sensing organ;

Be used for determining the signal processing unit of described input radio frequency signal with respect to the phase shift of described output radiofrequency signal, intraorganic blood flow has been represented in described phase shift; With

Use the blood flow computer of the blood flow in the described phase in-migration computer official, wherein said blood flow computer can move to use the linear relationship between described phase shift and the blood flow to calculate blood flow.

6. system according to claim 5, wherein said signal processing unit comprises design and is configured to reduce or eliminates the envelope elimination unit of the which amplitude modulation of described input radio frequency signal, so that the input radio frequency signal of constant envelope to be provided.

7. system according to claim 6, wherein said envelope is eliminated the unit design and is configured to keep the phase place modulation of described input radio frequency signal.

8. system according to claim 6, wherein said envelope is eliminated the unit and is comprised limiting amplifier.

9. system according to claim 5, wherein said signal processing unit comprises:

Blender with described radio-frequency signal generator and described a plurality of electrodes to the small part telecommunication, described mixer design and be configured to described output radiofrequency signal is mixed with described input radio frequency signal is to provide the blended radiofrequency signal of having represented blood flow; With

The electronic circuit that is used for the part of the described blended radiofrequency signal of filtering is with the signal to noise ratio of the remainder that increases described blended radiofrequency signal.

10. system according to claim 9, wherein said blender can move so that radio frequency and and radiofrequency difference to be provided.

11. system according to claim 10, wherein said electronic circuit comprise be used for the described radio frequency of filtering and low pass filter.

12. system according to claim 9, wherein said electronic circuit comprises the analog amplify circuit of the described remainder that is used to amplify described blended radiofrequency signal.

13. system according to claim 9, wherein said electronic circuit comprises the digitized digital converter of described remainder that is used for described blended radiofrequency signal.

14. system according to claim 9, wherein said design of electronic circuits and be configured to minimize of the sensitivity of described input radio frequency signal to the impedance contrast between the organ of described a plurality of electrodes and object.

15. system according to claim 14, wherein said electronic circuit comprises that at least one is characterized as the differential amplifier of its impedance greater than the described impedance contrast between the organ of described a plurality of electrodes and object.

16. system according to claim 9, comprise that further the described remainder that is used to use described blended radiofrequency signal calculates the data processor of at least one amount, select the group of described at least one amount blood flow and arterial blood flow in comprising stroke volume, cardiac output, encephalocoele.

17. system according to claim 16, wherein said arterial blood flow is selected from the group that comprises following item: arteria carotis externa blood flow, arteria carotis interna blood flow, ulnar artery blood flow, radial artery blood flow, brachial artery blood flow, common iliac artery blood flow, external iliac artery blood flow, back tibial artery blood flow, preceding tibial artery blood flow, peroneal artery blood flow, lateral plantar artery blood flow, medial plantar artery blood flow and deep plantar artery blood flow.

18. system according to claim 16, comprise further and communicate by letter with described data processor and can move pacemaker that wherein said data processor is programmed to according to the value of described at least one amount described pacemaker be carried out Electronic Control with the heart rate of control object.

19. system according to claim 16, comprise further and communicate by letter with described data processor and can move that wherein said data processor is programmed to according to the value of described at least one amount described drug administration device be carried out Electronic Control with drug administration device to the object administration medicine.

20. system according to claim 16 further comprises and communicates by letter with described data processor and can move to increase described kinemic heart-assist device.

21. system according to claim 20, wherein said heart-assist device comprises design and is configured to limit the expansible reinforcement members of the part of heart tissue, therefore to increase cardiac output.

22. system according to claim 9, the number of wherein said a plurality of electrodes are chosen as described input radio frequency signal is separated with selected at least one influence from the group that comprises posture change influence, breathing influence and motion effects.

23. system according to claim 9, wherein said a plurality of electrodes comprise two electrodes.

24. system according to claim 9, wherein said a plurality of electrodes comprise three electrodes.

25. system according to claim 9, wherein said a plurality of electrodes comprise four electrodes.

It is irrelevant 26. system according to claim 9, the partial design at least of wherein said a plurality of electrodes and being configured to have the constant sensitivity of the signal of telecommunication by described electrode transmission with the orientation of described electrode on object.

27. system according to claim 9, the comprising design and be configured to twine the conductive material at least one prolongation of small part of the outward sense of object to small part of wherein said a plurality of electrodes, the constant sensitivity of the signal of telecommunication by described electrode transmission is had nothing to do with the orientation of described electrode on described outward sense to have.

28. system according to claim 27, wherein said a plurality of electrodes comprise the attachment material to small part.

29. system according to claim 27, wherein said outward sense is selected from the group that comprises breast, buttocks, thigh, neck, head, arm, abdomen, lower limb and foot.

30. system according to claim 9, further comprise detector to the small part telecommunication with described a plurality of electrodes, with the primary importance that is used for detected object and the voltage between the second position, and be used for generating described input radio frequency signal in response to described voltage, wherein said input radio frequency signal has been represented the impedance and/or the hematodinamics reactance of organ.

31. system according to claim 30, comprise that further at least one is used for the pick off of the described voltage of sensing, described at least one sensor design and being configured to generate its amplitude be in the organ, from organ or to the signal of the function of the blood flow of organ.

32. system according to claim 30, wherein said electronic circuit comprises the differentiator that is used to carry out at least one time diffusion, with described impedance that organ is provided and/or each derivative of hematodinamics reactance.

33. system according to claim 32, wherein said derivative is selected from the group that comprises first derivative and second dervative.

34. system according to claim 32, wherein said differentiator is selected from the group that comprises digital differentiator and analog differentiation device.

35. system according to claim 9 further comprises the display device that is used to show blood flow.

36. system according to claim 35, wherein said display device can show the blood flow as time function.

37. system according to claim 9, wherein said signal to noise ratio increase is 10dB at least.

38. system according to claim 9, wherein said signal to noise ratio increase is 20dB at least.

39. the method for the intraorganic blood flow of measuring object, this method comprises:

Generate the output radiofrequency signal;

With the input radio frequency signal of described output radio signal transmission to organ and sensing organ; With

Determine described input radio frequency signal with respect to the phase shift of described output radiofrequency signal and use blood flow in the described phase in-migration computer official, wherein said calculating is based on the linear relationship between described phase shift and the blood flow.

40. according to the described method of claim 39, the proportionality coefficient of wherein said linear relationship comprises the paradoxical expansion ejection time of the heart of object.

41., further comprise the which amplitude modulation that reduces or eliminate described input radio frequency signal, so that the input radio frequency signal of constant envelope to be provided according to the described method of claim 39.

42. according to the described method of claim 41, wherein said reduction or eliminate the phase place modulation that described which amplitude modulation comprises the input radio frequency signal of keeping described constant envelope.

43., wherein carry out the reduction or the elimination of described which amplitude modulation by limiting amplifier according to the described method of claim 41.

44. according to the described method of claim 39, wherein further comprise described output radiofrequency signal is mixed with described input radio frequency signal, so that the blended radiofrequency signal of having represented blood flow to be provided, and the part of the described blended radiofrequency signal of filtering is with the signal to noise ratio of the remainder that increases described blended radiofrequency signal.

45. according to the described method of claim 44, wherein said mixing comprises provides radio frequency and and radiofrequency difference.

46. according to the described method of claim 45, wherein by design and be configured to the described radio frequency of filtering and low pass filter carry out the described part of the described blended radiofrequency signal of described filtering.

47., further comprise simulation amplification to the described remainder of described blended radiofrequency signal according to the described method of claim 44.

48., further comprise digitized to the described remainder of described blended radiofrequency signal according to the described method of claim 44.

49. according to the described method of claim 44, wherein carry out the described transmission of described output radiofrequency signal and the described sensing of described input radio frequency signal, and this method comprises further and minimizes the sensitivity of described input radio frequency signal to the impedance contrast between the organ of described a plurality of electrodes and object by a plurality of electrodes.

50. according to the described method of claim 49, wherein said input radio frequency signal minimizes the described sensitivity of described impedance contrast described and is characterized as its impedance by at least one and carries out greater than the differential amplifier of described impedance contrast.

51. according to the described method of claim 44, comprise that further the described remainder that uses described blended radiofrequency signal calculates at least one amount, select the group of described at least one amount blood volume and arterial blood flow in comprising stroke volume, cardiac output, encephalocoele.

52. according to the described method of claim 51, wherein said arterial blood flow is selected from the group that comprises following item: arteria carotis externa blood flow, arteria carotis interna blood flow, ulnar artery blood flow, radial artery blood flow, brachial artery blood flow, common iliac artery blood flow, external iliac artery blood flow, back tibial artery blood flow, preceding tibial artery blood flow, peroneal artery blood flow, lateral plantar artery blood flow, medial plantar artery blood flow and deep plantar artery blood flow.

53., further comprise heart rate according to the value control object of described at least one amount according to the described method of claim 51.

54., wherein carry out the heart rate of described control object by pacemaker according to the described method of claim 53.

55. according to the described method of claim 51, further comprise the value of using described at least one amount select the amount of medicine and type and to the object administration described amount with medicine described type.

56., further comprise the surgery approach position of the part that is provided to the object heart and keep the expansible reduction of heart of the described part of described heart, to increase described cardiac output according to the described method of claim 51.

57., wherein carry out the described input radio frequency signal of the described output radiofrequency signal of described transmission to organ and sensing organ by a plurality of electrodes being connected to subject's skin according to the described method of claim 44.

58. according to the described method of claim 57, the number of wherein said a plurality of electrodes is chosen as separates described input radio frequency signal with selected at least one influence from the group that comprises posture change influence, breathing influence and motion effects.

59. according to the described method of claim 57, wherein said a plurality of electrodes comprise two electrodes.

60. according to the described method of claim 57, wherein said a plurality of electrodes comprise three electrodes.

61. according to the described method of claim 57, wherein said a plurality of electrodes comprise four electrodes.

62. according to the described method of claim 57, wherein said a plurality of electrodes described is connected to has constant sensitivity and irrelevant with the orientation of described electrode on object to the signal of telecommunication by described electrode transmission.

63. according to the described method of claim 57, the comprising design and be configured to twine the conductive material at least one prolongation of small part of the outward sense of object to small part of wherein said a plurality of electrodes, the constant sensitivity of the signal of telecommunication by described electrode transmission is had nothing to do with the orientation of described electrode on described outward sense to have.

64. according to the described method of claim 63, wherein said outward sense is selected from the group that comprises breast, buttocks, thigh, neck, head, arm, abdomen, lower limb and foot.

65. according to the described method of claim 44, further comprise the primary importance of detected object and the voltage between the second position and generate described input radio frequency signal in response to described voltage, wherein said input radio frequency signal has been represented the impedance and/or the hematodinamics reactance of organ.

66. according to the described method of claim 65, further comprise and carry out at least one time diffusion, provide each derivative of the described impedance and/or the hematodinamics reactance of organ with this.

67. according to the described method of claim 66, wherein said derivative is selected from the group that comprises first derivative and second dervative.

68. according to the described method of claim 66, the described process of carrying out selecting from the group that comprises numerical differentiation and analog differentiation of wherein said time diffusion realizes.

69., further comprise and use display device to show blood flow according to the described method of claim 44.

70. according to the described method of claim 69, wherein said display device can show the blood flow as time function.

71. according to the described method of claim 44, wherein said signal to noise ratio increase is 10dB at least.

72. according to the described method of claim 44, wherein said signal to noise ratio increase is 20dB at least.

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